MATURITAS

JOURNAL OF THE
CLIMACTERIC 8
POSTMENOPAUSE
Maturitas 20 (1995) 151-154

The role of prolactin in the menopause

M. Metka*, G. Holzer, H. Raimann, G. Heytmanek, B. Hartmann, Ch. Kurz

Ist Department of Obstetrics and Gynecology, University of Vienna, Department for Endocrinological Gynecology Spitalgasse 23,
A-1090 Vienna, Austria

Received 22 October 1993; revision received 18 March 1994; accepted 18 March 1994

Abstract

Within a study on menopausal discomforts, 2322 women were seen for the first time at the Outpatients Department
for Climacteric Disturbances and Prophylaxis of Osteoporosis at our clinic. Amongst routine hormonal examination
we measured prolactin levels. We found hyperprolactinemia in 23 women. Furthermore, in 224 women who initially
had normal hPRL values, an estrogen-gestagen replacement therapy was administered and within this we found a signi-
ficant increase of the prolactin levels (P < 0.005). The role of prolactin in the climacteric period as well as the mecha-
nism of the estrogen effect upon prolactin secretion are subjects of discussion.

Keyword: Menopause; Hormone replacement therapy; Hyperprolactinemia; hPRL screening

1. Introduction measured from the beginning. The objectives of

The problems of the menopause and in particu-
lar of the postmenopause have increasingly gained
importance over the last years. This is clearly evi-
denced by rising frequency of visits to the outpa-
tients department of our clinic (‘Outpatients
Department for Climacteric Disturbances and
Prophylaxis of Osteoporosis’). The background of
that boom might be found in the increased life ex-
pectancy, in the increased standards of living and
also in the awareness of new possibilities of
diagnostics, prophylaxis and therapy.
In our department, in addition to the common
hormone parameters, prolactin levels were
* Corresponding author.
this study were to point out the potential impor-
tance of prolactin screening in postmenopausal
women on one hand as well as the changes of pro-
lactin levels during hormonal replacement therapy
on the other hand.
2. Materials and methods
2.1. Patients
From January 1985 until December 1991, 2322
women (aged 51.4 f 6.4 years) were seen at our
outpatients department for climacteric complaints
(Table 1). Besides a detailed anamnesis, performed
with a computer-aided questionnaire including the
Kupperman’s score, a gynecologic examination, a
basic mammography (which were brought along

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152 h-f. Metka et al. /Maturitas 20 (1995) 151-154

by the patients) as well as a bone densitometry
were conducted; the hormonal examination forms
a focal point of the clarification. In the course of
this investigation, we included serum levels of thy-
roid hormones (Ts, T4, TSH, TBG), 17&estradiol,
the gonadotropines (LH, FSH) as well as pro-
lactin.
None of the patients included in our study had
undergone medication with estrogen and/or any
other steroid substitution either before or during
the time of the study. In order to objectively
analyze the influence of a hormone replacement
therapy upon the prolactin level we compiled two
groups after the first examination - a therapy
group and a control group. Both groups consisted
of women who had neither an endocrinological
disease nor had they been subjected to hyster-
ectomy.
All women in the therapy and control groups
were postmenopausal. Postmenopause was detin-
ed by the fact that these women have had no bleed-
ing for more than one year and FSH > 25 mu/ml.
Women in the therapy group (224 patients, aver-
age age: 52.2 f 7.1, hPRL < 20 ng/ml) had
agreed to long-term hormone replacement con-
sisting of a combination of conjugated estrogens
(dosage: 0.625 mg from days l-30) with the
gestagen medrogestone (5 mg from days 20-30).
Women from the control group (147 patients -
average age: 49.4 f 5.6) took no hormones.
2.2. Serum examination
The serum levels of LH and FSH were measured
with radioimmunoassay using agents of SORIN
(Sorin Biomedica, Saluggia, Italy - LH) and of
BEHRING (Behringwerke AG, Marburg, Ger-
many - FSH). Serum hPRL concentrations were
determined by a one step immunoassay (Enzymun,
Boehringer - Mannheim) calibrated against the
2nd International WHO standard 75/504. The 17&
estradiol serum levels were measured using the
solid-phase coated tube method using reagents of
DPC (Diagnostic Products Corp., LA, California,
USA). The intra- and interassay variation coeffic-
ient in all methods was 5%- 11%.
Blood samples were drawn during the first week
of the estrogen intake. Because of circadian fluc-
tuation in prolactin the blood samples were taken
in the morning between 08:OO and 09:OOh. The
maximum standard range for women (hPRL -
Standard of the NIH, Bethesda, Maryland) is 20
@ml of serum. Consequently, we divided the pa-
tients into four groups: group one formed by
women with normal hPRL levels (O-20 ng/ml),
group two with hPRL-values from 20-40 @ml,
group three consisted of women with hyperprolac-
tinemia with levels from 40 rig/ml, and group four
consisted of women with hPRL levels of more than
100 @ml.
2.3. Statistical analysis
The statistical evaluations were performed with
the Student’s t-test.
3. Results
3.1. Hormonal evaluations
The serum prolactin levels of the screening in
2322 women resulted in a hyperprolactinemea with
values in excess of 40 rig/ml in 139 patients, of
which 23 women had hPRL levels of more than
100 ng/ml. These patients were further examined
with a computer tomography scanner at a
neurosurgical department. A total of 993 women
displayed levels between 20 and 40 ng/ml whilst the
majority of patients (n = 1167) were within the
standard range (Tables 1 and 2).
3.2. During hormone replacement
We monitored the hPRL level after 3 months of
hormone replacement therapy (n = 224). Thereby
we found a statistically significant increase of the
prolactin levels from 8.33 f 5.87 @ml before re-
placement therapy to 11.94 @ml (P < 0.05). In
Table I
Serum hormone levels
Hormone Level
LH (mu/ml) 28 it I
FSH (mu/ml) 31 * 13
E2 (pg/ml) 38 -f 22
T3 (ng/ml) 1.4 iz 0.6
T, (ng/ml) 89 zt 16
TSH (pUlm1) 2.1 f I
TBG (&I00 ml) 21.1 f 10.2
 M. Metka et al. / Maturitas 20 (199s) ISI-154 153

Table 2 of the hPRL level in normoprolactinemic women

Patient characterisation [ 1,12,21,23]. Replacement over an extended period
Therapy group Control group is also said to have no influence on hPRL levels in
(n = 24) (II = 147) women after the natural menopause; likewise an
application over a 3 month period in oophorec-
Age (years) 52.2 f 7.1 49.40 ?? 5.60
Height (cm) 164.2 zt 13.23 158.6 f 13.22
tomized patients [ 151.
Weight (kg) 63.8 f 15.73 66.0 f 15.62 It has been demonstrated that in postmeno-
Menarche (years) 13.8 f 1.30 13.80 f 2.16 pausal women an increase of the prolactin level oc-
Menopause (years) 50.88 f 3.70 48.83 f 4.28 curs if estrogen is administered [3]. This increase
seems to be dose-related. Under long-term therapy
with estrogen implants, a 13% increase of the
hPRL in postmenopausal women is reported,
contrast, the values in patients of the control which, however, does not lead to hyperprolac-
group remained unchanged (8.44 f 4.56 @ml). tinemia [l]. Higher basic hPRL levels are also
Six months after treatment we performed a third known in patients with prolactinomas after estro-
measurement. Results obtained displayed a further gen stimulation [23].
statistically significant increase of the prolactin The regulation of the axis ‘hypothalamus -
levels (average value 13.03 f 5.04 rig/ml, P < hypophysis - ovary’ with the aid of estrogen -
0.05). The values of the control group after 6 gestagen replacement, also known from the thy-
months were 7.92 f 5.23 @ml. roid gland, is likely to facilitate a ‘normalisation’
of prolactin levels (and an approximation, respec-
4. Discussion tively, towards values which are normal in the
reproductive phase).
Estrogens and especially 17/3-estradiol have an Summarizing our investigations we conclude
important modulating effect on prolactin secretion that there is only a light increase of the prolactin
[6]. This effect occurs on two levels: at the hypo- values. Under therapy with conjugated estrogen
thalamus and the hypophysis. Although the mech- we could not observe increases of the initial values
anism of the estrogen-induced increase of the of the hPRL level up to three or four times as pro-
hPRL level remains still uncertain, the direct effect claimed in other studies. It should be stressed that
on the prolactin secretion or the lactotrophic hy- we have no indications that oral contraceptives
perplasia might play a certain role. The direct (i.e. estrogens in low doses) produce prolac-
effect of estrogens upon prolactin-producing cells tinomas [4,6,13].
is explained through binding to specific In contrast to other studies from larger subject
cytoplasmatic receptors [ 141. groups our data demonstrate unambiguously that
There is only little knowledge regarding the amongst hormone replacement therapy with estro-
physiological effect of prolactin, particularly gens (in the present case 0.625 mg conjugated es-
within the postmenopause. With the beginning of trogens) there is a statistically significant increase
menopause a reduction of prolactin levels was of the prolactin values even within the period of 3
noticed, which subsequently increased again [ 191. months. After 6 months the results are more evi-
However the hPRL values remain unchanged if dent. It should, however, be stressed that any in-
the menopause is reached naturally; in surgically creases were within the standard range.
induced menopause higher hPRL levels were If we consider that the fatal inductions of a pro-
found than throughout the luteal phase of normal nounced hyperprolactinemia and of a prolac-
cycling women [15]. tinoma, respectively, are possible by estrogens
The literature does not present a uniform pic- [5,8,9,11,16,22,23], it must be said that the collec-
ture in the case of postmenopausal estrogen re- tive sample of 23 hyperprolactinemias recorded by
placement. Some studies quote that a short-term means of the prolactin screening absolutely
replacement will not produce significant changes justifies the screening. In these cases, hormone re-
154 hf. Metka et al. /Maturitas
placement has of course not been carried out and
the patients have been subjected to further exami-
nations.
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